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Alexander Becher, Tim Eiseler, Marc Porzner, Paul Walther, René Keil, Susanne Bobrovich, Mechthild Hatzfeld, Thomas Seufferlein
We here report a novel function of the armadillo protein p0071 (also known as PKP4) during transport mediated by the KIF3 transport complex. Secretion of chromogranin A and matrix metallopeptidase 9 from pancreatic neuroendocrine tumor cells or pancreatic cancer cells, respectively, was substantially reduced following knockdown of p0071. Vesicle tracking indicated that there was impaired directional persistence of vesicle movement upon p0071 depletion. This suggests a disturbed balance between plus- and minus-end directed microtubule transport in cells lacking p0071...
October 1, 2017: Journal of Cell Science
Li Jiang, Beatrice M Tam, Guoxing Ying, Sen Wu, William W Hauswirth, Jeanne M Frederick, Orson L Moritz, Wolfgang Baehr
In Caenorhabditis elegans, homodimeric [kinesin family (KIF) 17, osmotic avoidance abnormal-3 (OSM-3)] and heterotrimeric (KIF3) kinesin-2 motors are required to establish sensory cilia by intraflagellar transport (IFT) where KIF3 and KIF17 cooperate to build the axoneme core and KIF17 builds the distal segments. However, the function of KIF17 in vertebrates is unresolved. We expressed full-length and motorless KIF17 constructs in mouse rod photoreceptors using adeno-associated virus in Xenopus laevis rod photoreceptors using a transgene and in ciliated IMCD3 cells...
December 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Li Jiang, Yuxiao Wei, Cecinio C Ronquillo, Robert E Marc, Bradley K Yoder, Jeanne M Frederick, Wolfgang Baehr
Anterograde intraflagellar transport (IFT) employing kinesin-2 molecular motors has been implicated in trafficking of photoreceptor outer segment proteins. We generated embryonic retina-specific (prefix "emb") and adult tamoxifen-induced (prefix "tam") deletions of KIF3a and IFT88 in adult mice to study photoreceptor ciliogenesis and protein trafficking. In (emb)Kif3a(-/-) and in (emb)Ift88(-/-) mice, basal bodies failed to extend transition zones (connecting cilia) with outer segments, and visual pigments mistrafficked...
May 15, 2015: Journal of Biological Chemistry
Nicolas Forcioli-Conti, Sandra Lacas-Gervais, Christian Dani, Pascal Peraldi
The primary cilium is an organelle present in most of the cells of the organism. Ciliopathies are genetic disorders of the primary cilium and can be associated with obesity. We have studied the primary cilium during adipocyte differentiation of human adipose stem cells (hASC). We show here that the size of the primary cilium follows several modifications during adipocyte differentiation. It is absent in growing cells and appears in confluent cells. Interestingly, during the first days of differentiation, the cilium undergoes a dramatic elongation that can be mimicked by dexamethasone alone...
February 27, 2015: Biochemical and Biophysical Research Communications
Hui-Qun Phang, Jing-Ling Hoon, Soak-Kuan Lai, Yukai Zeng, Keng-Hwee Chiam, Hoi-Yeung Li, Cheng-Gee Koh
The kinesin motors are important in the regulation of cellular functions such as protein trafficking, spindle organization and centrosome separation. In this study, we have identified POPX2, a serine-threonine phosphatase, as an interacting partner of the KAP3 subunit of the kinesin-2 motor. The kinesin-2 motor is a heterotrimeric complex composed of KIF3A, KIF3B motor subunits and KAP3, the non-motor subunit, which binds the cargo. Here we report that the phosphatase POPX2 is a negative regulator of the trafficking of N-cadherin and other cargoes; consequently, it markedly influences cell-cell adhesion...
February 15, 2014: Journal of Cell Science
Yasuhiro Funahashi, Takashi Namba, Shin Fujisue, Norimichi Itoh, Shinichi Nakamuta, Katsuhiro Kato, Akiko Shimada, Chundi Xu, Wei Shan, Tomoki Nishioka, Kozo Kaibuchi
Axon formation is one of the most important events in neuronal polarization and is regulated by signaling molecules involved in cytoskeletal rearrangement and protein transport. We previously found that Partition-defective 3 (Par3) is associated with KIF3A (kinesin-2) and is transported into the nascent axon in a KIF3A-dependent fashion. Par3 interacts with the Rac-specific guanine nucleotide-exchange factors (GEFs) Tiam1/2, which activate Rac1, and participates in axon formation in cultured hippocampal neurons...
August 14, 2013: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Prajwol Pathak, Valeria Zilberman, Boris Avezbakiyev, Vladimir Gotlieb
Hairy cell leukemia is a rare cancer of the blood. The occurrence of hairy cell leukemia with another very rare genetic disorder makes us question whether it is just a coincidence. This article reports the first case of hairy cell leukemia in a patient with situs inversus totalis in western literature. There have been studies into the pathogenesis of situs inversus totalis that suggest it is caused by the failure of embryonic cells to properly rotate during embryogenesis. On the molecular level, the nodal cilia, which are responsible for embryonic rotation, are built by transport through the KIF3 complex - a kinesin superfamily of molecular motors...
May 2013: Future Oncology
Eva D'Amico, Stéphanie Gayral, Claude Massart, Jacqueline Van Sande, Jeremy F Reiter, Jacques E Dumont, Bernard Robaye, Stéphane Schurmans
Kinesins, including the kinesin 2/KIF3 molecular motor, play an important role in intracellular traffic and can deliver vesicles to distal axon terminals, to cilia, to nonpolarized cell surfaces or to epithelial cell basolateral membranes, thus taking part in the establishment of cellular polarity. We report here the consequences of kinesin 2 motor inactivation in the thyroid of 3-week-old Kif3a(Δ)(/flox) Pax8(Cre/)(+) mutant mice. Our results indicate first that 3-week-old Pax8(Cre/)(+) mice used in these experiments present minor thyroid functional defects resulting in a slight increase in circulating bioactive TSH and intracellular cAMP levels, sufficient to maintain blood thyroxine levels in the normal range...
June 2013: Journal of Molecular Endocrinology
Jason R Bader, Brandon W Kusik, Joseph C Besharse
Multiple proteins are targeted to photoreceptor outer segments (OSs) where they function in phototransduction. Intraflagellar transport (IFT), a highly conserved bidirectional transport pathway occurring along the microtubules of the ciliary axoneme has been implicated in OS trafficking. The canonical anterograde motor for IFT is the heterotrimeric kinesin II or KIF3 complex. Previous work from our laboratory has demonstrated a role for an additional kinesin 2 family motor, the homodimeric KIF17. To gain a better understanding of KIF17 function in photoreceptor OS we utilized transgenic zebrafish expressing zfKIF17-GFP to assess the localization and dynamics of zfKIF17...
December 15, 2012: Vision Research
Xiaowei Yu, Hai Wen, Jianhua Cao, Binbin Sun, Tao Ding, Ming Li, Hao Wu, Long Long, Xinghai Cheng, Guangfei Xu, Feng Zhang
The KIF3 subunit KIF3B was proved to be associated with mitosis. It has been known to be engaged in intracellular transport of neurons. To elucidate the certain expression and biological function in central nervous system, we performed an acute spinal cord contusion injury model in adult rats. Western blot analysis indicated a marked upregulation of KIF3B after spinal cord injury (SCI). Immunohistochemistry revealed wide distribution of KIF3B in spinal cord, including neurons and glial cells. Double immunofluorescent staining for proliferating cell nuclear antigen and phenotype-specific markers showed increases of KIF3B expression in proliferating microglia and astrocytes...
February 2013: Journal of Molecular Neuroscience: MN
Raphaël Gaudin, Bruna Cunha de Alencar, Mabel Jouve, Stefano Bèrre, Emmanuel Le Bouder, Michael Schindler, Aditi Varthaman, François-Xavier Gobert, Philippe Benaroch
Macrophages are long-lived target cells for HIV infection and are considered viral reservoirs. HIV assembly in macrophages occurs in virus-containing compartments (VCCs) in which virions accumulate and are stored. The regulation of the trafficking and release of these VCCs remains unknown. Using high resolution light and electron microscopy of HIV-1-infected primary human macrophages, we show that the spatial distribution of VCCs depended on the microtubule network and that VCC-limiting membrane was closely associated with KIF3A+ microtubules...
October 29, 2012: Journal of Cell Biology
Jonathan M Scholey
The sensory outer segments (OS) of vertebrate retinal photoreceptors, which detect photons of light, resemble the distal segments of Caenorhabditis elegans sensory cilia, which detect chemical ligands that influence the chemotactic movements of the animal. Based on fluorescence microscopy assays performed in sensory cilia of living, transgenic "wild type" and mutant C. elegans, combined with in vitro motility assays using purified motors, we have proposed that two types of kinesin-2 motor, heterotrimeric kinesin-II and homodimeric OSM-3, cooperate to build amphid and phasmid sensory cilia on chemosensory neurons...
December 15, 2012: Vision Research
Nobutaka Hirokawa, Yosuke Tanaka, Yasushi Okada
The establishment of left-right asymmetry during development of vertebrate embryos depends on leftward flow in the nodal cavity. The flow is produced by the rotational movement of the posteriorly tilted nodal cilia. However, it remains poorly understood how the nodal cilia are tilted posteriorly, and how the directionality of the flow is translated into gene expression patterns in the embryo. Recent studies have identified signaling molecules involved in these processes. First, planar cell polarity signaling has been shown to be involved in the posterior positioning of the basal bodies of nodal cilia, which leads to the posterior tilting of their rotation axes...
February 2012: Current Opinion in Cell Biology
Lihai Zhang, Terrence Gavin, Anthony P DeCaprio, Richard M LoPachin
2,5-Hexanedione (HD) intoxication is associated with axon atrophy that might be responsible for the characteristic gait abnormalities, hindlimb skeletal muscle weakness and other neurological deficits that accompany neurotoxicity. Although previous mechanistic research focused on neurofilament triplet proteins (NFL, NFM, NFH), other cytoskeletal targets are possible. Therefore, to identify potential non-NF protein targets, we characterized the effects of HD on protein-protein interactions in cosedimentation assays using microtubules and NFs prepared from spinal cord of rats intoxicated at different daily dose rates (175 and 400 mg/kg/day)...
September 2010: Toxicological Sciences: An Official Journal of the Society of Toxicology
Yasushi Okada, Nobutaka Hirokawa
Mammalian left-right determination is a good example of how multiple cell biological processes coordinate in the formation of a basic body plan, but until recently its mechanism was totally elusive. In the past 10 years, molecular genetic studies of kinesin and dynein motor proteins, live-cell imaging techniques, and theoretical studies of fluid mechanics revealed unexpected mechanisms of left-right determination. The leftward movement of fluid at the ventral node, called nodal flow, is the central process in symmetry breaking on the left-right axis...
2009: Methods in Cell Biology
Tomohiro Haruki, Yoshihiko Maeta, Sei-ichi Nakamura, Takashi Sawata, Tetsu Shimizu, Kiyoshi Kishi, Shigeto Miyasaka, Hiroyuki Maeta, Keisuke Morimoto, Iwao Taniguchi
Situs inversus totalis (SIT) is a relatively rare congenital anomaly, occurring at an incidence of 1 in 10 000-50 000 live births. Although there are some case reports of SIT with the presence of cancer, there are few reports on the relationship between SIT and cancer. However, the recent phylogenetic investigations of this condition suggest that this may be linked to the development and progression of cancer on the molecular level. The key elements are one of the intracellular motor proteins, the KIF3 complex, and the cell-adhesion factors N-cadherin and beta-catenin...
2010: Surgery Today
Nobutaka Hirokawa, Yosuke Tanaka, Yasushi Okada
Mammalian left-right determination is a good example for how multiple cell biological processes coordinate in the formation of a basic body plan. The leftward movement of fluid at the ventral node, called nodal flow, is the central process in symmetry breaking on the left-right axis. Nodal flow is autonomously generated by the rotation of posteriorly tilted cilia that are built by transport via KIF3 motor on cells of the ventral node. How nodal flow is interpreted to create left-right asymmetry has been a matter of debate...
July 2009: Cold Spring Harbor Perspectives in Biology
René Keil, Christina Kiessling, Mechthild Hatzfeld
P0071 (plakophilin-4) is a member of the p120ctn subfamily of armadillo proteins that are essential for cell contact formation. Additionally, p0071 plays a role in cytokinesis, in which it regulates local activation of RhoA together with Ect2. Because spatiotemporal regulation is required for progression through cytokinesis, we analyzed when and how p0071 is targeted to the midbody to induce RhoA activation. We show that Ect2 precedes p0071 accumulation at the midbody and that targeting is mediated by different motor proteins...
April 15, 2009: Journal of Cell Science
Masahiro Nagao, Hideaki Hayashi
The expression of hippocalcin, a calcium-sensor protein of the recoverin family, and mixed lineage kinase 2 (MLK2) in Lewy bodies (LBs) was immunohistochemically examined in patients with Parkinson's disease (PD). Hippocalcin and MLK2 were colocalized in the halo of LBs, and neither protein was detected in normal pigmented neurons. Since hippocalcin binds to the C-terminal region of MLK2 [Nagata K., Puls A, Futter C, Aspenstrom P, Schaefer E, Nakata T et al., The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3...
June 15, 2009: Journal of the Neurological Sciences
N Tanuma, M Nomura, M Ikeda, I Kasugai, Y Tsubaki, K Takagaki, T Kawamura, Y Yamashita, I Sato, M Sato, R Katakura, K Kikuchi, H Shima
Recent studies have demonstrated essential functions for KIF3, a microtubule-directed protein motor, in subcellular transport of several cancer-related proteins, including the beta-catenin-cadherin(s) complex. In this study, we report identification of the protein-phosphatase Dusp26 as a novel regulator of the KIF3 motor. Here we undertake yeast two-hybrid screening and identify Kif3a, a motor subunit of the KIF3 heterotrimeric complex, as a novel Dusp26-binding protein. Co-immunoprecipitation and colocalization experiments revealed that Dusp26 associates not only with Kif3a, but also with Kap3, another subunit of the KIF3 complex...
February 5, 2009: Oncogene
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